Failure to maintain stem cells with age is associated with conditions such as tissue degeneration and increased susceptibility to tissue damage in many organisms, including humans. This proposal addresses how aging affects stem cells using the C. elegans germ line as a model. Studies using C. elegans and its germ line have revealed conserved mechanisms of aging and stem cell biology, therefore this proposal combines a well-established genetic model for aging studies and a well- defined, accessible stem cell system, providing a unique opportunity to dissect the effects of aging on stem cell dynamics. We will determine the cellular mechanisms underlying stem cell depletion and its prevention by the insulin/IGF-signaling pathway. We will also determine the specific tissue requirements for this particular anti-aging effect of the insulin/IGF-signaling pathway. These pilo studies will lay the groundwork for future work. PUBLIC HEALTH RELEVANCE: Aging impacts reproduction. This application follows from our discovery that the proliferative stem cell population of the C. elegans germ line is depleted with age in a manner dependent on the conserved insulin/IGF signaling pathway. Our studies will likely benefit human health since the cellular and molecular mechanisms underlying aging and stem cell dynamics are evolutionarily conserved.